Many substances obtained from modern drug discovery are problematic because of insufficient bioavailability. Such molecules often exhibit very low aqueous solubility and limited solubility in oils. Furthermore many substances exhibit significant food effects, i.e., when drugs and certain foods are taken at the same time they can interact in ways that diminish the effectiveness of the ingested drug or reduce the absorption of food nutrients. Additionally, vitamin and herbal supplements taken with prescribed medication can result in adverse reactions.
Some examples of how foods and drugs can interact include:                Food can speed up or slow down the action of a medication.        Impaired absorption of vitamins and minerals in the body.        Stimulation or suppression of the appetite.        Drugs may alter how nutrients are used in the body.        
NK-1 receptor antagonists of formula I have been described in commonly owned EP 1,035,115 and U.S. Pat. No. 6,297,375
wherein    R is lower alkyl, lower alkoxy, halogen or trifluoromethyl    R1 is halogen or hydrogen; and when p is 1, R1 may in addition to the above substituents be taken together with R to form —CH═CH—CH═CH—;    R2 and R2′ are each independently hydrogen, halogen, trifluoromethyl, lower alkoxy or cyano;and when n is 1, R2 and R2′ may in addition to the above substituents form —CH═CH—CH═CH—, unsubstituted or substituted by one or two substituents selected from lower alkyl or lower alkoxy;    R3 and R3′ are hydrogen, lower alkyl or taken together with the attached carbon atom form a cycloalkyl group;    R4 is hydrogen, —N(R5)(CH2)nOH, —N(R5)S(O)2-lower alkyl, —N(R5)S(O)2-phenyl, —N═CH—N(R5)2, —N(R5)C(O)R5,
    R5 is hydrogen, C3-6-cycloalkyl, benzyl, or lower alkyl;    R6 is hydrogen, hydroxy, lower alkyl, —(CH2)nCOO—(R5), —N(R5)CO-lower alkyl, hydroxy-lower alkyl, —(CH2)nCN, —(CH2)nO(CH2)nOH, —CHO or a 5- or 6-membered heterocyclic ring containing from 1 to 4 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur, and with one of the carbon atoms in said ring being unsubstituted or substituted with an oxo group, which heterocyclic ring is directly bonded or bonded via an alkylene group to the remainder of the molecule;
is a cyclic tertiary amine which may contain one additional heteroatom selected from the group consisting of oxygen, nitrogen, or sulfur, wherein any sulfur present in the ring is thio or can be oxidized to sulfoxide or sulfur dioxide by which said cyclic tertiary amine is directly attached to the remainder of the molecule or is attached through the linker    —(CH2)nN(R5)—;    X is —C(O)N(R5)—, —(CH2)mO—, —(CH2)mN(RS)—, —N(R5)C(O)—, or —N(R5)(CH2)m—;    n, p, and q are each independently 1 to 4; and    m is 1 or 2;    and pharmaceutically acceptable acid addition salts thereof.
These compounds exist in crystalline form, which is practically insoluble in water (for example <0.0001 mg/ml) and in simulated gastric fluid (for example 0.08 mg/ml) at 25° C. They are active NK1 receptor antagonists, useful for the treatment of CNS disorders, such as depression, anxiety and emesis.